Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities

Cells die by a variety of mechanisms. Terminally differentiated cells such as neurones die in a variety of disorders, in part, via parthanatos, a process dependent on the activity of poly ( ADP ‐ribose)‐polymerase ( PARP ). Parthanatos does not require the mediation of caspases for its execution, but is clearly mechanistically dependent on the nuclear translocation of the mitochondrial‐associated apoptosis‐inducing factor ( AIF ). The nuclear translocation of this otherwise beneficial mitochondrial protein, occasioned by poly ( ADP ‐ribose) ( PAR ) produced through PARP overactivation, causes large‐scale DNA fragmentation and chromatin condensation, leading to cell death. This review describes the multistep…